The broad, long-term objective of the present project is the development of a viable scheme for the total synthesis of the aglycone of the potent, natural anti-cancer agents esperamicin and calichemicin. Specifically in this proposal, model studies are planned to determine the feasibility of assembling the cyclodecaenediyne segment of the aglycone through a convergent sequence, involving two symmetric acyclic intermediates. Because the pharmacological activity of esperamicin and calichemicin resides mainly in the chemistry of the aglycone, and also because related cyclic enediynes have been found to posses similar biological activity as the bicyclic aglycone, the cyclodecaenediyne, which is the target of this present study is expected to show similar chemical reactivity. Specific model studies are planned to address (a) the stereospecific synthesis of the intermediate trans, trans-3,4-dibromo-2,4-hexadien-1,6- diol dipyranyl ether; (b) the determination of the best method for generating stable dilithium derivative of this dibromide and (c) establishment of the optimal conditions for a 1:1 adduct-the cyclodecaenediyne-from the dilithium derivative and the enediyne dialdehyde, cis-4-en-2,6-diyn-1,8-octadial-hyde. The preparation of the two intermediates for the assembly of the cyclodecaenediyne exploits various type of palladium-catalyzed reactions. The symmetric nature of these intermediates and the convergent scheme reduces the number of steps of the cyclodecaenediyne-an advanced intermediate in the overall scheme for the aglycone. The cyclodecaenediyne product expected from this study will have the same hybridization in all its carbons as the ten-membered ring of the natural aglycone. It will also contain functional groups and side chains at appropriate points for further elaboration to the aglycone in later stages. Molecular models show that the geometry of the chains and functional groups on the cyclodecaenediyne will be favorable, after routine side chain elaboration, for an intramolecular cyclization to complete the bicyclic skeleton. The resulting bicyclic skeleton is expected to possess adequate functionalization and activation to generate the different C-O bonds of the aglycone.